Burisch J, Munkholm P (2013) Inflammatory bowel disease epidemiology. Curr Opin Gastroenterol 29:357–362

Article  CAS  PubMed  Google Scholar 

Bressler B, Marshall JK, Bernstein CN, Bitton A, Jones J, Leontiadis GI, Panaccione R, Steinhart AH, Tse F, Feagan B (2015) Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus. Gastroenterology 148:1035-1058. e1033

Article  PubMed  Google Scholar 

Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF (2017) Ulcerative colitis. Lancet 389:1756–1770. https://doi.org/10.1016/s0140-6736(16)32126-2

Article  PubMed  Google Scholar 

Ko CW, Singh S, Feuerstein JD, Falck-Ytter C, Falck-Ytter Y, Cross RK (2019) AGA clinical practice guidelines on the management of mild-to-moderate ulcerative colitis. Gastroenterology 156:748–764. https://doi.org/10.1053/j.gastro.2018.12.009

Article  PubMed  Google Scholar 

Raine T, Bonovas S, Burisch J, Kucharzik T, Adamina M, Annese V, Bachmann O, Bettenworth D, Chaparro M, Czuber-Dochan W, Eder P, Ellul P, Fidalgo C, Fiorino G, Gionchetti P, Gisbert JP, Gordon H, Hedin C, Holubar S, Doherty G (2022) ECCO guidelines on therapeutics in ulcerative colitis: medical treatment. J Crohns Colitis 16:2–17. https://doi.org/10.1093/ecco-jcc/jjab178

Article  PubMed  Google Scholar 

Burri E, Maillard MH, Schoepfer AM, Seibold F, Van Assche G, Rivière P, Laharie D, Manz M (2020) Treatment algorithm for mild and moderate-to-severe ulcerative colitis: an update. Digestion 101(suppl 1):2–15. https://doi.org/10.1159/000504092

Article  CAS  PubMed  Google Scholar 

Ursini F, Russo E, Pellino G, D’Angelo S, Chiaravalloti A, De Sarro G, Manfredini R, De Giorgio R (2018) Metformin and autoimmunity: a “new deal” of an old drug. Front Immunol 9:1236

Article  PubMed  PubMed Central  Google Scholar 

Foretz M, Guigas B, Bertrand L, Pollak M, Viollet B (2014) Metformin: from mechanisms of action to therapies. Cell Metab 20:953–966

Article  CAS  PubMed  Google Scholar 

Crowley MJ, Diamantidis CJ, McDuffie JR, Cameron CB, Stanifer JW, Mock CK, Wang X, Tang S, Nagi A, Kosinski AS, Williams JW Jr (2017) Clinical outcomes of metformin use in populations with chronic kidney disease, congestive heart failure, or chronic liver disease: a systematic review. Ann Intern Med 166:191–200. https://doi.org/10.7326/m16-1901

Article  PubMed  PubMed Central  Google Scholar 

Kulkarni AS, Gubbi S, Barzilai N (2020) Benefits of metformin in attenuating the hallmarks of aging. Cell Metab 32:15–30

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bharath LP, Nikolajczyk BS (2021) The intersection of metformin and inflammation. Am J Physiol-Cell Physiol 320:C873–C879

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hua Y, Zheng Y, Yao Y, Jia R, Ge S, Zhuang A (2023) Metformin and cancer hallmarks: shedding new lights on therapeutic repurposing. J Transl Med 21:403

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pal B, Ghatak N, Hossain CM (2025) Metformin as a potential neuroprotective agent that influence Parkinson’s disease. Neurol Sci 46:4805–4818. https://doi.org/10.1007/s10072-025-08370-w

Article  PubMed  Google Scholar 

Pantazopoulos D, Papachristou S, Gouveri E, Papi M, Papazoglou D, Papanas N (2025) Metformin: old drug, new therapeutic potential in the skin? A brief narrative review. Adv Ther 42:3606–3620. https://doi.org/10.1007/s12325-025-03256-x

Article  PubMed  PubMed Central  Google Scholar 

Huang Z, Li J, Chen H, Yu D, Sun S (2023) The efficacy of metformin for the treatment of psoriasis: a meta-analysis study. Postepy Dermatol Alergol 40:606–610. https://doi.org/10.5114/ada.2023.130524

Article  PubMed  PubMed Central  Google Scholar 

Xue Y, Zhang H, Sun X, Zhu MJ (2016) Metformin improves ileal epithelial barrier function in interleukin-10 deficient mice. PLoS ONE 11:e0168670. https://doi.org/10.1371/journal.pone.0168670

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sutherland LR, Martin F, Greer S et al (1987) 5-Aminosalicylic acid enema in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology 92:1894–1898

Article  CAS  PubMed  Google Scholar 

Pabla BS, Schwartz DA (2020) Assessing severity of disease in patients with ulcerative colitis. Gastroenterol Clin 49:671–688

Article  Google Scholar 

El-Haggar SM, Hegazy SK, Maher MM, Bahgat MM, Bahaa MM (2024) Repurposing metformin as adjuvant therapy in patients with ulcerative colitis treated with mesalamine: a randomized controlled double-blinded study. Int Immunopharmacol 138:112541. https://doi.org/10.1016/j.intimp.2024.112541

Article  CAS  PubMed  Google Scholar 

Binsaleh AY, El-Haggar SM, Hegazy SK, Maher MM, Bahgat MM, Elmasry TA, Alrubia S, Alsegiani AS, Eldesoqui M, Bahaa MM (2025) The adjunctive role of metformin in patients with mild to moderate ulcerative colitis: a randomized controlled study. Front Pharmacol 16:1507009. https://doi.org/10.3389/fphar.2025.1507009

Article  CAS  PubMed  PubMed Central  Google Scholar 

Petrov JC, Desai AA, Kochhar GS, Crosby SK, Kinnucan JA, Picco MF, Hashash JG, Farraye FA (2025) Metformin is associated with improved inflammatory bowel disease outcomes in patients with type 2 diabetes mellitus: a propensity-matched cohort study. Inflamm Bowel Dis 31:1237–1247. https://doi.org/10.1093/ibd/izae147

Article  PubMed  Google Scholar 

Li X, Xiang Z, Wang X, He H, Xu M, Tan C, Wu X, Zhang J, Dong W (2025) Metformin attenuates colitis via blocking STAT3 acetylation by reducing acetyl-CoA production. J Adv Res. https://doi.org/10.1016/j.jare.2025.03.058

Article  PubMed  PubMed Central  Google Scholar 

Ke H, Li F, Deng W, Li Z, Wang S, Lv P, Chen Y (2021) Metformin Exerts Anti-inflammatory and Mucus Barrier Protective Effects by Enriching Akkermansia muciniphila in Mice With Ulcerative Colitis. Front Pharmacol 12:726707. https://doi.org/10.3389/fphar.2021.726707

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wanchaitanawong W, Thinrungroj N, Chattipakorn SC, Chattipakorn N, Shinlapawittayatorn K (2022) Repurposing metformin as a potential treatment for inflammatory bowel disease: evidence from cell to the clinic. Int Immunopharmacol 112:109230. https://doi.org/10.1016/j.intimp.2022.109230

Article  CAS  PubMed  Google Scholar 

Rubin DC, Shaker A, Levin MS (2012) Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer. Front Immunol 3:107. https://doi.org/10.3389/fimmu.2012.00107

Article  PubMed  PubMed Central  Google Scholar 

Saber MM, Galal MA, Ain-Shoka AA, Shouman SA (2016) Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. BMC Cancer 16:126. https://doi.org/10.1186/s12885-016-2157-9

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lee SY, Lee SH, Yang EJ, Kim EK, Kim JK, Shin DY, Cho ML (2015) Metformin ameliorates inflammatory bowel disease by suppression of the STAT3 signaling pathway and regulation of the between Th17/Treg balance. PLoS ONE 10:e0135858. https://doi.org/10.1371/journal.pone.0135858

Article  CAS  PubMed  PubMed Central  Google Scholar 

Al-Dwairi A, Alqudah M, Al-Shboul O, Alfaqih M, Alomari D (2018) Metformin exerts anti-inflammatory effects on mouse colon smooth muscle cells in vitro. Exp Ther Med 16:985–992. https://doi.org/10.3892/etm.2018.6222

Article  CAS  PubMed